About this Research Topic
Cells release into the extracellular environment vesicles of varying sizes, collectively termed
extracellular vesicles (EVs), which are generated both through the endosomal pathway and from the
plasma membrane. EVs carry a repertoire of biological molecules including nucleic acids, proteins,
lipids, and carbohydrates and transport their cargo between cells locally or at a distance, acting as
important mediators of intercellular communication.
Over the last years a number of immunomodulatory molecules like Damage Associated Molecular
Patterns (DAMPs) have been described to be transported by EVs. In normal conditions DAMPs are
harbored intracellularly, but they can be exposed on the cell surface or secreted upon stress, injury, cell
death, thereby becoming able to bind to cognate receptors on immune cells. Thus, DAMPs can directly
activate innate immune cells like dendritic cells (DCs), macrophages, neutrophils and natural killer (NK)
cells and indirectly stimulate T lymphocyte responses by promoting DC maturation..
Emerging evidence has shown the presence of distinct DAMPs into EVs including the heat shock protein
(HSP) molecules, the high-mobility group box 1 (HMGB1), but also dsDNA, RNA and miRNAs, all able
to engage different Pattern Recognition Receptors (PRRs). In this scenario, persistent and dysregulated
stimuli triggered by DAMPs lead to inflammatory response that can contribute to the development of
several immune-mediated disorders including autoimmune diseases.
On the other hand, the presence of DAMPs on cancer-derived EVs could be effective to promote tumor
progression via inflammation and immunosuppression or to induce tumor inhibition/rejection via
immunogenic cell death and other mechanisms, depending on the immune cell populations localized in
the tumor microenvironment.
The aim of this Research Topic is to gather a comprehensive overview of the immunomodulatory action
of DAMPs associated to EVs and their importance in the pathogenesis of a variety of immune-mediated
diseases. We’ll also explore their role in cancer immunosurveillance. We envisage that a better
knowledge of the role of DAMPs on EVs is needed to identify new therapeutic targets for drug
Therefore, we welcome the submission of Reviews and Original Research articles covering but not
limited to the following topics:
• EVs and DAMPs.
• EVs in the pathogenesis of immune-mediated diseases.
• EVs and autoimmune disease
• EVs between innate and adaptive immunity
• DAMPs-containing EVs in cancers
Important Note: All contributions to this Research Topic must be within the scope of the section and journal to which they are submitted, as defined in their mission statements. Frontiers reserves the right to guide an out-of-scope manuscript to a more suitable section or journal at any stage of peer review.